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Three researchers from the University of California, Davis, are among the scientists selected to receive Individual Biomedical Research Awards from The Hartwell Foundation this year. The awards recognize early-stage, innovative and cutting-edge biomedical research that has the potential to benefit children in the U.S. and beyond.

Lin Tian and Candice Clay are two of the researchers to receive Hartwell Foundation awards in 2013.

Each award provides $100,000 of direct support per year for three years, as well as videoconferencing equipment to facilitate mentorship with the Foundation and collaboration with other award recipients. UC Davis also received a Hartwell Fellowship to fund one postdoctoral candidate of its choice that exemplifies the values of the foundation. The fellowship provides support for two years at $50,000 in direct cost per year.

Individual Biomedical Research Award winners are Lin Tian and Angela Gelli, both in the UC Davis School of Medicine. Candice Clay, a postdoctoral researcher at the California National Primate Research Center at UC Davis, was selected by UC Davis to receive the Hartwell Fellowship.

The Hartwell Foundation designated UC Davis as one of its Top Ten Centers for Biomedical Research for the third year in a row. The prestigious designation, held by only a few of the nation’s top research facilities, places UC Davis in company with other stalwarts such as Cornell, Duke and Johns Hopkins universities and St. Jude Children's Research Hospital. Including Gelli and Tian, the Foundation has honored seven UC Davis scientists and engineers with Individual Biomedical Research Awards since 2009.

Understanding disrupted neural networks and mental retardation

Tian, assistant professor in the Department of Biochemistry and Molecular Medicine, conducts research focused on the nature of mental retardation, specifically Down syndrome, which affects one out of every 700 to 800 babies born in the United States. Tian will study the changes leading to altered physical and neurocognitive growth in Down syndrome with the goal of developing new therapies to correct the most common symptom, mental retardation. Her work will specifically focus on the role of glial cells in the formation of neural networks during brain development and explore how functional interactions within the network change with the progression of the disease.

“Glial cells guide the development of neuronal networks by ‘listening and talking’ to neighboring neurons in the developing brain,” Tian said. “The progression of Down syndrome has long been suspected to be caused by changes in this circuitry. Aberrant neural interactions are thought to play a key role in many other cognitive disorders, as well, including epilepsy, schizophrenia and autism. By growing in cell culture neurons and glial cells derived from typically developing individuals as well as those with Down syndrome, I hope to better understand the nature of mental retardation and how genetic identity is linked to the structure and function of neural networks.”

Tian will monitor the neural networks formed in cell cultures to see if they closely resemble normal or disrupted connectivity and function in the brain. To understand how abnormal logic at the neural network level could relate to the Down syndrome brain, she will use optical sensors (also known as optogenetic sensors) in this model system to track calcium signaling, an important measure of network dynamics. She also will use computational modeling to describe the logic of the interactions between neurons and glial cells and attempt to target the observed network communication defects with specific drug combinations identified through a high-throughput screening of several million compounds.

“I became very interested in studying neurological diseases in children when I became pregnant in 2009,” she said. “Fortunately, my son does not have any neurological diseases. But since becoming a mother, I am now personally vested in helping find answers to these diseases. This award from The Hartwell Foundation will allow me to become established in this area of study.”

Improving drug delivery in diseases of the brain

Gelli, an associate professor in the Department of Pharmacology, conducts research focused on understanding Cryptococcus neoformans, a human fungal pathogen that is the leading cause of fungal meningitis worldwide and a significant cause of AIDS-related infections. Gelli is interested in understanding how the pathogenbreaches the blood-brain barrier to enter the brain, where it causes life-threatening infection in patients, especially those with compromised immune systems.

Gelli believes that the organism’s ability to invade the central nervous system also serves as a model for developing new approaches to deliver therapeutic drugs to the brain for the treatment of brain cancer, including glioblastoma multiforme, an aggressive malignant primary tumor in children that is nearly 100 percent fatal.

“The inability to deliver therapeutic drugs into the brain is the single most important reason attributed to the high mortality in children with glioblastoma,” Gelli said. “Nearly 100 percent of known chemotherapeutic drugs cannot cross the blood-brain barrier, which normally protects the brain from harmful substances and pathogens. Although different approaches for getting chemotherapy into the brain have been suggested, many are far too invasive or toxic, resulting in irreversible damage to surrounding, healthy brain tissue.

“By coupling the brain-penetrating mechanisms of C. neoformans to novel formulations of drug-loaded nano-size non-toxic particles, I hope to create a novel, drug delivery system that will deliver therapeutic drugs specifically to the brain. If successful, the paradigm-shifting technology would have an enormous impact on the survival of afflicted children. The platform technology could also revolutionize treatments for other brain disorders,” she said.

“I believe children should be given every opportunity to flourish and for me that means improving the health of kids by developing new approaches to deliver lifesaving drugs to the brain for the treatment of childhood brain tumors,” Gelli said. “There is nothing more devastating than a life of a child cut short because of this awful disease. The award from The Hartwell Foundation allows me the opportunity to fully pursue the research and develop the technology that will hopefully boost the quality of life of afflicted children.”

Postdoctoral fellowship

Clay earned her doctorate in immunology from UC Davis and will investigate why young children are so vulnerable to lung infections, such as bronchiolitis and respiratory syncytial virus (RSV), the most common cause of severe lower respiratory tract disease among infants and young children worldwide. Her work is aimed ultimately at developing treatments to help children fight off these infections.

“I know of so many friends and family members whose children have had to go to the hospital due to respiratory problems like bronchitis or respiratory syncytial virus,” said Clay. “These diseases can have a lasting impact on the health of these children for the rest of their lives. Even though it impacts so many people, very little is known about how to cure these diseases, which is why I want to focus my research in this area.”

Clay will work with Lisa Miller, associate professor of anatomy, physiology and cell biology in the UC Davis School of Veterinary Medicine and associate director of research at the California National Primate Research Center; and Frederic Chedin, associate professor of molecular and cellular biology, College of Biological Sciences and the UC Davis Comprehensive Cancer Center. Chedin received a Biomedical Research Award from The Hartwell Foundation in 2011.

In making the selection, the Foundation takes into account the interest the institution has in children's health, the presence of a medical school and biomedical engineering program, and the quality of ongoing biomedical research. It also considers the commitment to collaborate, provide encouragement and give technical support to the researchers.

“The Hartwell Foundation seeks to inspire innovation and achievement by offering individual researchers an opportunity to realize their professional goals. We believe that philanthropy is a serious responsibility and that wealth appropriately used is an essential mechanism for improving the state of mankind,” said Fred Dombrose, president of The Hartwell Foundation. “Through a unique and selective funding process, we provide financial support to stimulate discovery in early-stage biomedical research that we hope will benefit children of the United States. UC Davis has been a key partner with the foundation in accomplishing this goal.”

In the Hartwell competition, all nominees submit a detailed research proposal, are personally interviewed and make a formal presentation of their proposed research. In selecting awardees, The Hartwell Foundation takes into account the nature of the proposed innovation, the extent to which a strategic or translational approach might promote rapid clinical application of research results, the supportive role and extent of collaboration in the proposed research, the institutional commitment to provide encouragement and technical support to the investigator, and the extent to which funding the investigator will make a difference.

About The Hartwell Foundation

Located in Memphis, Tenn., The Hartwell Foundation seeks to inspire innovation and achievement by offering individual researchers an opportunity to realize their professional goals. The Foundation believes that philanthropy is a serious responsibility and that wealth appropriately used is an essential mechanism for improving the state of mankind. Through a unique and selective funding process, the Foundation provides financial support to stimulate discovery in early-stage biomedical research that has potential to benefit children of the United States. For more information about The Hartwell Foundation, visit www.thehartwellfoundation.org.

About UC Davis

For more than 100 years, UC Davis has engaged in teaching, research and public service that matter to California and transform the world. Located close to the state capital, UC Davis has more than 33,000 students, more than 2,500 faculty and more than 21,000 staff, an annual research budget of nearly $750 million, a comprehensive health system and 13 specialized research centers. The university offers interdisciplinary graduate study and more than 100 undergraduate majors in four colleges — Agricultural and Environmental Sciences, Biological Sciences, Engineering, and Letters and Science. It also houses six professional schools — Education, Law, Management, Medicine, Veterinary Medicine and the Betty Irene Moore School.